STUDY OF INHERITED NEUROLOGICAL DISEASES

遗传性神经系统疾病的研究

• 批准号: 7604961
• 负责人: KEVIN M FLANIGAN
• 金额: $ 0.82万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604961
• 关键词: Animal Disease Models; Biological; Biological Models; Biopsy; CADASIL; Cell Line; Clinical; Complement; Computer Retrieval of Information on Scientific Projects Database; DNA; Diagnosis; Disease; Duchenne muscular dystrophy; Dystrophin; Encephalopathies; Exons; Fibroblasts; Funding; Gene Mutation; Genes; Genetic Transcription; Genomics; Grant; Inherited; Institution; Lymphocyte; Messenger RNA; Mitochondria; Modeling; Molecular; Muscle; Mutation; Myoblasts; Neurologic; Neuromuscular Diseases; Nonsense Codon; Patients; Protein Analysis; Proteins; Protocols documentation; Purpose; RNA Splicing; Red Fiber; Research; Research Personnel; Resources; Sampling; Skin; Source; Standards of Weights and Measures; Syndrome; Testing; Tissues; Transcript; Translational Research; United States National Institutes of Health; Variant; design; human disease; mdx mouse; nervous system disorder; novel; protein expression

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The diagnosis of some neurologic diseases often requires tissue biopsy. Two relatively easily accessible tissues, muscle and skin, are routinely and safely biopsied for clinical purposes. Such clinically-indicated biopsies are usually performed in the setting of neuromuscular disease, but this is not always the case; as examples, muscle biopsies are performed for the confirmation of mitochondrial encephalopathy (in which ragged-red fibers may be seen), and skin biopsies for the diagnosis of CADASIL. In the research setting, muscle and skin biopsies provide unique resources for study, as discussed below. Genes involved in inherited neuromuscular disorders are often expressed only in muscle. In many inherited diseases, no alternate model systems of disease exist for study. Conversely, in some diseases where animal models exist, they are inadequate for the testing of hypotheses related to patient-specific gene mutations. One example of this is found in Duchenne Muscular Dystrophy (DMD). The mdx mouse is accepted as a standard model of DMD, due to the presence of a premature stop codon mutation within exon 23 of the dystrophin gene. However, the human disease is due to a wide variety of dystrophin mutations, and is associated with wide variation in dystrophin protein levels and in dystrophin alternate mRNA transcripts. Characterization of dystrophin mRNA and protein requires muscle biopsy. This protocol is designed to complement two other current protocols: Translational Research in the Dystrophinopathies (GCRC03-32; IRB#10966) and Molecular Characterization of Inherited Neurologic Disease (GCRC 04-07; IRB#6697). In each of these projects, studies of genomic DNA derived from subject lymphocyte samples has led to hypotheses regarding molecular mechanisms that may be tested only by further studies of tissue-specific gene transcription or splicing, or protein expression The objective of this study is: To provide biological materials necessary for the molecular characterization of novel or rare neurological and neuromuscular syndromes, including: a. Tissues for RNA, DNA, and protein analysis b. Cultured cell lines for experimental purposes (myoblasts and fibroblasts)

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 某些神经系统疾病的诊断通常需要组织活检。 两种相对容易获得的组织，肌肉和皮肤，通常用于临床目的。 这种临床指示的活检通常是在神经肌肉疾病的情况下进行的，但并非总是如此。例如，进行肌肉活检以确认线粒体脑病（可以看到衣衫式红色纤维），并进行皮肤活检以诊断卡达西尔。 在研究环境中，肌肉和皮肤活检提供了独特的研究资源，如下所述。 与遗传性神经肌肉疾病有关的基因通常仅在肌肉中表达。 在许多遗传疾病中，没有其他疾病模型的研究。 相反，在某些存在动物模型的疾病中，它们不足以检测与患者特异性基因突变有关的假设。 一个例子是在Duchenne肌肉营养不良（DMD）中发现的。 由于肌营养不良蛋白基因的外显子23中存在过早的终止密码子突变，因此MDX小鼠被接受为DMD的标准模型。 然而，人类疾病是由于多种肌营养不良蛋白突变引起的，并且与肌营养不良蛋白蛋白水平和肌营养不良蛋白交替的mRNA转录本的变化有关。 肌营养不良蛋白mRNA和蛋白质的表征需要肌肉活检。 该方案旨在补充其他两种当前的方案：肌营养不良的转化研究（GCRC03-32； IRB＃10966）和遗传神经疾病的分子表征（GCRC 04-07; IRB＃6697）。 在这些项目中的每个项目中，对受试者淋巴细胞样品得出的基因组DNA的研究已导致有关分子机制的假设 这项研究的目的是： 提供新型神经系统或神经肌肉综合征的分子表征所必需的生物学材料，包括： 一个。 用于RNA，DNA和蛋白质分析的组织 b。 用于实验目的的培养细胞系（成肌细胞和成纤维细胞）